DİYABET HASTALIĞINDA OSTEOPROTEGERİN (OPG) PROTEİNİ T950C GEN POLİMORFİZMİNİN İNCELENMESİ

Year 2011, Volume: 1 Issue: 1, 40 - 46, 25.10.2011

Burak Esen Selçuk Daşdemir Zeynep Çinçin Abdullah Özdemircan Bedia Çakmakoğlu

Abstract

Osteoprotegerin (OPG), TN F (tümör nekroz faktör) bağımlı ailenin bir üyesi ve NF-KB
ligandının (RANKL) reseptör aktivatörü ve NF-KB (RANK) reseptör aktivatörüdür. OPG
polimorfizmlerinin diyabet hastalığında risk arttırıcı faktörler olduğu, çeşitli çalışmalarla
gösterilmiştir. Biz çalışmamızda, PZR, RFLP ve agaroz jel elektroforezi yöntemlerini
kullanarak 77 tip II diyabet hastası ve 83 sağlıklı kontrol üzerinde OPG T950C gen
polimorfîzmini araştırdık.
OPG T950C genotip dağılımları; hasta grubunda %41,56 TT, %15,58 CC, %42,86 TC olarak
bulunurken, kontrol grubunda ise %31,62 TT, % 14,70 CC, %53,68 TC olarak saptanmıştır.
Hasta ve kontrol grupları arasında OPG T950C genotip ve allel frekansları açısından
istatistiksel anlamlı bir fark gözlemlenmemiştir (p > 0.05). Bununla birlikte, hasta grubunda
OPG T950C CC genotipi frekansının myokard infarktüsü (MI) varlığında 3,15 kat, sol
ventrikül hipertrofisi (LVH) varlığında 1,38 kat, aile hikayesinde DM (+) bireylerde 4 kat,
erkeklerde 2,6 kat, hipertansiflerde 2,33 kat, aile hikayesinde koroner arter hastalığı (KAH)
(+) hastalarda 2,3 kat arttığını gözlemlenmiştir. KAH gehşiminde etkili faktörlerin varlığında
CC genotipinin frekansındaki artış bu genotipin bir risk faktörü olabileceğini düşündürmektedir.
Sonuç olarak, çalışmamızda OPG T950C polimorfizminin diyabet hastalarında KAH
gelişiminde etkili olabileceği belirlenmiştir.

References

• 1.Georg Schert, MD; Stefan Kiechl, MD; Kurt Redlich, MD; Friedrich Oberhollenzer, MD; Siegfried Weger, MD; Georg Egger, MD; Agnes Mayr, MD; Josef Jocher, MD; Qingbo Xu, MD; Peter Pietschmann, MD; Steven Teitelbaum, MD; Josef Smolen, MD; Johann Willeit, MD. Soluble RANKL and Risk of Nontraumatic Fracture. JAMA. 2004; 291: 1108-1113.
• 2.0hmori R., Momiyama R., Nagano M., Taniguchi H , Nataka N., Kato R., Egashira T., Arakawa K , Nakamura H., Ohsuzu F. Association between osteoprotegerin gene polymorphism and coronary artery disease in Japanese men. Current Opinion in Lipidology 2006; 17(5): 562-596.
• 3.American Diabetes Association: Diagnosis and classification of Diabetes Mellitus. Diabetes Care 2010; 33: 62-69.
• 4. Atkinson M, MacLaren N. The pathogenesis of insulin dependent diabetes. N Eng J Med 1994; 331: 1428¬ 1436.
• 5. Alberti KG, Zimmet PZ ve ark. Definition, diagnosis and classification of diabetes mellitus and its complications part 1: diagnosis and classification of diabetes mellitus provisional report of a who consultation. Diabetic Medicine 2004; 15(7): 539¬ 553.
• 6.Simonson DC, Ferrannini E, Bevilacqua S, Smith D, Barrett E, Carlson R, ve ark Mechanism of improvement in glucose metabolism after chronic glyburide therapy. Diabetes 1984; 33: 838-845.
• 7. Wing RR, Blair EH, Bononi P, Marcus MD, Watanabe R, Bergman RN. Caloric restriction per se is a significant factor in improvements in glycémie control and insulin sensitivity during weight loss in obese NIDDM patients. Diabetes Care 1994; 17: 30-36.
• 8. Beckman JA, Ganz J, Creager MA, Ganz P, Kinlay S. Relationship of clinical presentation and calcifications culprit coronary artery stenoses. Arterioscler. Thromb. Vase. Biol. 2001; 21: 1618-1622.
• 9. Harris M, Zimmet P. Classification of diabetes mellitus and other categories of glucose intolerance. Internationa Textbook of Diabetes Mellitus 1997; 2: 9-23.
• 10. Zimmet PZ. Kelly West Lecture 1991: challenges in diabetes epidemiology: from West to the rest. Diabetes Care 1992; 15: 232-252.
• 11.Harris MI, Cowie CC, Stern MP, Boyko ES, Reiber GE, Bennett PH. Diabetes in America, 2nd edn. 1995; 95-1468.
• 12. Miller SA, Dykes DD and Polesky HF: A simple saltingout procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16: 1215,1988.
• 13. Brandström H., Stiger F., Lind L., Kahan T, Melhus H , Kindmark A. A single nucleotide polymorphism in the promoter region of the human gene for osteoprotegerin is related to mascular morphology and function. Biochemical and Biophysical Research Communications. 2002; 293(1): 13-17.
• 14. Bağnaçık N : Tarn, komplikasyonlara yaklaşım ve tedavi konsonsus el kitabı, Novo Nordisk diabet servisi yayınları, İstanbul 1997.
• 15. King H, Rewers M, Zimmet P, Dowse G. WHO Adhoc Reporting Group: global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults. Diabetes Care 1993; 16: 157-177.
• 16. Bağnaçık N. Î.Ü.Cerrahpaşa Tıp Fakültesi Sürekli Tıp Eğitimi Etkinlikleri.Diabetes Mellitus Sempozyumu 1997 18 -19 Aralık, İstanbul s.9-18.
• 17. American Diabetes Association: Role of cardiovasculer risk factor in prevention and treatment of macrovasculer disease in diabetes. Diabetes care, 1989; 12: 573 - 579.
• 18. Rasmussen LM, Ledet T. Osteoprotegerin and diabetic macroangiopathy. Horm. Metab. Res 2000; 1: 90-94.
• 19.Stefan Kiechl, Georg Schett, Gregor Wenning, Kurt Redlich, Martin Oberhollenzer, Agnes Mayr, Peter Santer, Josef Smolen, Werner Poewe, Johann Willeit. Osteoprotegerin Is a Risk Factor for Progressive Atherosclerosis and Cardiovascular Disease. Circulation, 2004; 109: 2175 - 2180.
• 20.Schoppet M ve ark. Increased osteoprotegerin serum levels in men with coronary artery disease. J Clin Endocrinol Metab. 2003; 88(3): 1024-8.
• 21.Rasmussen Lm ve ark. Plasma Osteoprotegerin levels are associated with glycaemic status, systolic bloodd pressure, kidney function and cardiovascular morbidity in type 1 diabetic patients, Eur. J. Endocrinol 2006; 154: 75-81.
• 22. Browner WS ve ark. Associations of serum osteoprotegerin levels with diabetes, stroke , bone density, fractures and mortality in elderly women. J. Clin. Endocrinol. Metab. 2001; 86: 631-637.
• 23. Knudsen S ve ark. Increased plasma concentrations of osteoprotegerin in type 2 diabetic patients with microvascular complications. Eur. J. Endocrinol. 2003; 149: 39-42.
• 24. Pazalluoli ve ark. Osteoprotegerin and B-type natriuretic peptide in non-ST elevation acute coronary syndromes: Relation to coronary artery narrowing and plaques number. Clinica Chimica Acta 2008; 391: 74-79.
• 25.Soufi ve ark. Osteoprotegerin Gene Polymorphisms in Men with Coronary Artery Disease; The Journal of Clinical Endocrinology & Metabolism 2004; 89(8): 3764-3768.
• 26. Brandstr6m ve ark. A single nucleotide polymorphism in the promoter region of the osteoprotegerin gene is related to intima-media thickness of the carotid artery in hypertensive patients. The Swedish irbesartan left ventricular hypertrophy investigation vs atenolol (SILVHIA). Blood Pressure 2004;13(3): 152-157.
• 27. Rhee ve ark. The relationship between four single nucleotide polymorphisms in the promoter region of the osteoprotegerin gene and aortic calcification or coronary artery disease in Koreans. Clinical Endocrinology 2006; 64: 689-697.
• 28. A. Avignon, A. Sultan, C. Piot, S. Elaerts, J.R Cristol, A.M. Dupuy. Osteoprotegerin is associated with silent coronary artery disease in high-risk but asymptomatic type 2 diabetic patients, Diabetes Care 2005; 28: 2176-2180.
• 29. Akinci B ve ark. Serum osteoprotegerin is associated with carotid intima media thickness in women with previous gestational diabetes. Diabetes research and clinical practice 2008; 82: 172-178.
• 30. Browner W.S.ve ark. Associations of Serum Osteoprotegerin Levels with Diabetes, Stroke, Bone Density, Fractures, and Mortality in Elderly Women. The Journal of Clinical Endocrinology & Metabolism 2001; 86(2): 631-637.
• 31. Xiang G ve ark. Changes of osteoprotegerin before and after insulin therapy in type 1 diabetic patients. Diabetes Research and Clinical Practice 2007; 76: 199-206